Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2012-03, Vol.6 (3), p.e1567
Main Authors: Mire, Chad E, Miller, Andrew D, Carville, Angela, Westmoreland, Susan V, Geisbert, Joan B, Mansfield, Keith G, Feldmann, Heinz, Hensley, Lisa E, Geisbert, Thomas W
Format: Article
Language:English
Subjects:
Aerosols
Animals
Biological & chemical terrorism
Biology
Dosage and administration
Ebola virus
Ebolavirus - immunology
Ebolavirus - pathogenicity
Encephalitis, Viral - pathology
Genetic aspects
Genetic Vectors
Genomes
Glycoproteins
Glycoproteins - genetics
Glycoproteins - immunology
Immunization
Infections
Infectious diseases
Macaca
Male
Marburgvirus - immunology
Marburgvirus - pathogenicity
Measles
Medicine
Pathogens
Prevention
Primate Diseases - pathology
Primates
Properties
Proteins
Public health
Risk factors
RNA polymerase
RNA viruses
Stomatitis
Tropical diseases
Vaccines
Vaccines, Attenuated - administration & dosage
Vaccines, Attenuated - adverse effects
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - adverse effects
Vaccines, Synthetic - genetics
Vaccines, Synthetic - immunology
Vesiculovirus - genetics
Vesiculovirus - pathogenicity
Viral Proteins - genetics
Viral Proteins - immunology
Viral vaccines
Viral Vaccines - administration & dosage
Viral Vaccines - adverse effects
Viral Vaccines - genetics
Viral Vaccines - immunology
Virulence (Microbiology)
Viruses
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Items that cite this one
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Description
Summary:The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0001567